Individuals who have a genetic variation associated with slower caffeine metabolism appear to have an increased risk of non-fatal heart attack associated with higher amounts of coffee intake, according to a study in the March 8 issue of JAMA.

Studies examining the association between coffee consumption and risk of myocardial infarction (MI heart attack) have been inconclusive. Coffee is a major source of caffeine, which is the most widely consumed stimulant in the world and has been implicated in the development of cardiovascular diseases such as heart attack, according to background information in the article. However, coffee contains a number of other chemicals that have variable effects on the cardiovascular system. It is not clear whether caffeine alone affects the risk of heart attack or whether other chemicals found in coffee may be responsible. Caffeine is metabolized primarily by the enzyme cytochrome P450 1A2 (CYP1A2) in the liver. Variations of the gene for this enzyme can slow or quicken caffeine metabolism. Carriers of the gene variant CYP1A2*1F allele are "slow" caffeine metabolizers, while individuals with the gene variant CYP1A2*1A allele are "rapid" caffeine metabolizers.

Ahmed El-Sohemy, Ph.D., of the University of Toronto, and colleagues conducted a study to determine whether gene variations of CYP1A2 modifies the association between consumption of caffeinated coffee and risk of nonfatal heart attack. The study included 2,014 case patients with a first acute nonfatal heart attack and 2,014 controls, living in Costa Rica between 1994 and 2004. The genotypes of the participants were determined. A food frequency questionnaire was used to assess the intake of caffeinated coffee.

Fifty-five percent of cases (n = 1,114) and 54 percent of controls (n = 1,082) were carriers of the slow *1F allele. For carriers of the slow *1F allele, those who drank 2 to 3 cups of coffee a day had a 36 percent increased odds of heart attack; thos'"/>

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